This project seeks to study electroretinogram (ERG) components that derive from the inner retina. The ERG is an extracellular response of the retina to stimulation by light and has traditionally been considered to reflect primarily outer retinal origins. As such it is currently used clinically in diagnosing human eye disease of the photoreceptors and structures nearby, such as in retinitis pigmentosa. However, more recently it has been appreciated that ERG components from the inner retina can also be recorded with appropriate stimuli, both within the retina using microelectrodes and clinically at the cornea. As a basic research tool, these responses may yield insight into how the inner retina functions. These proximal responses also greatly extend the scope of ERG testing and may provide an important new means to monitor human inner retinal pathology in glaucoma, diabetic and hypertensive retinopathy, and possibly amblyopia. Three ERG responses that have proximal retinal components will be investigated: the pattern-ERG, the photopic On- and Off-components, and the scotopic negative response below b-wave threshold. The aim is to characterize these responses in detail and to study the precise retinal depths of origin. The research strategy involves first studying the ERG in a convenient animal model, the cat. Intraretinal recording will be performed to identify the extra-cellular current source/sinks so that ultimately they can be linked to cell types. A second approach will evaluate how these ERG responses are changed in a cat model of inner retinal pathology; this will help clarify the origins of these components and may provide clues applicable in diagnosing human disease. Third, a correlated study of human ERG recordings will be performed to understand the normal response range; then, recordings will be evaluated in human ertinal disease to distinguish inner from outer retinal ERG sources in man and to begin clarifying the clinical value of these tests. The long term goal is to learn which retinal cells generate these responses and by what mechanism. This knowledge will increase our fundamental understanding of information processing in the retina, especially from a region that is otherwise difficult to monitor except by intracellular recordings. This knowledge will also increase the power of clinical ERG tests to help establish the locus of some human retinal diseases and to provide clues about their nature.